KRT7 Overexpression is Associated with Poor Prognosis and Immune Cell Infiltration in Patients with Pancreatic Adenocarcinoma

Figures & data

Figure 1 The expression level of KRT7 in PAAD and normal pancreas tissues. (A) The expression of KRT7 in PAAD (red) and normal pancreas tissue (gray) analyzed by GEPIA. (B) Meta-analyses of the KRT7 expression in PAAD samples analyzed by Oncomine. (C) The expression of KRT7 in various tumors analyzed by Oncomine. Red indicates high expression, and blue indicates low expression. (D) Immunohistochemical staining of KRT7 in PAAD tissues (a-c) and normal pancreas tissues (d-f) analyzed by the HPA database.

Table 1 Correlation Between KRT7 Expression and Clinicopathological Characteristics of PAAD

Variables	No. (n=178)	KRT7 High (n=89)	KRT7 Low (n=89)	P value
Age				0.33
≥60	123	58	65
<60	55	31	24
Gender				0.292
Female	80	36	44
Male	98	53	45
Histological type
Other subtype	25	7	18	0.046
Ductal type	147	80	67
Colloid carcinoma	4	1	3
Undifferentiated	1	0	1
Unknown	1	1	0
Grade				0.006
G1	31	9	22
G2	95	46	49
G3	48	33	15
G4	2	1	1
Gx	2	0	2
T classification				0.49
T1	7	3	4
T2	24	9	15
T3	142	75	67
T4	3	2	1
TX	1	0	1
Unknown	1	0	1
N classification				0.977
N0	49	24	25
N1	124	63	61
NX	4	2	2
Unknown	1	0	1
M classification				0.543
M0	80	39	41
M1	4	1	3
MX	94	49	45
Stage				0.588
I	21	9	12
II	147	76	71
III	3	2	1
IV	4	1	3
Unknown	3	1	2
Family history				0.13
No	47	29	18
Yes	64	29	35
Unknown	67	31	36
Chronic pancreatitis				1
No	12	64	65
Yes	913	7	6
Unknown	36	18	18
Diabetes history				0.418
No	109	59	50
Yes	38	17	21
Unknown	31	13	18
Alcohol history				0.131
No	64	26	38
Yes	102	55	47
Unknown	12	8	4
Adjuvant chemotherapy				0.584
No	45	25	20
Yes	90	44	46
Unknown	43	20	23
Adjuvant radiotherapy				0.679
No	102	51	51
Yes	32	18	14
Unknown	44	20	24

Table 2 Univariate and Multivariate Cox Regression Analysis of Overall Survival in PAAD Patients

Variables	Univariate		Multivariate
	P value	HR (95% CI)	P value	HR (95% CI)
Age
<60	Reference
≥60	0.144	1.403 (0.891–2.207)
Gender
Female	Reference
Male	0.35	0.823 (0.548–1.24)
Histological type
Ductal type	Reference
Other subtype	0.001	0.238(0.103–0.547)	0.009	0.28(0.107–0.734)
Colloid carcinoma	0.98	0.982(0.241–4.006)	0.464	0.515(0.087–3.035)
Undifferentiated	0.996	–	0.999	–
Unknown	0.996	–	0.999	–
Grade
G1	Reference
G2	0.042	1.993(1.027–3.87)	0.044	2.093(1.02–4.295)
G3+G4	0.008	2.575(1.283–5.17)	0.017	2.434(1.166–5.08)
Gx	0.592	1.754(0.225–13.66)	0.022	14.67(1.483–145.09)
T classification
T1+T2	Reference
T3+T4	0.026	2.053(1.089–3.871)	0.096	2.369(0.858–6.544)
TX	0.997	–	0.997	–
unknown	0.997	–	0.998	–
N classification
N0	Reference
N1	0.005	2.099(1.250–3.524)	0.057	2.047(0.979–4.277)
NX	0.972	1.027(0.234–4.501)	0.025	7.338(1.279–42.11)
Unknown	0.995	–	0.997	–
M classification
M0	Reference
M1	0.905	0.917(0.222–3.8)
MX	0.337	0.815(0.537–1.237)
Stage
I	Reference
II	0.032	2.349(1.077–5.123)	0.208	0.407(0.1–1.648)
III+IV	0.428	1.738(0.444–6.81)	0.371	0.457(0.082–2.542)
Unknown	0.996	–	–
Family history
No	Reference
Yes	0.637	1.138 (0.665–1.95)
Unknown	0.516	1.192(0.702–2.024)
Chronic pancreatitis
No	Reference
Yes	0.663	1.178 (0.563–2.466)
Unknown	0.453	1.209(0.736–1.985)
Diabetes history
No	Reference
Yes	0.798	0.93 (0.535–1.618)
Unknown	0.91	1.032(0.6–1.771)
Alcohol history
No	Reference
Yes	0.592	1.128 (0.727–1.75)
Unknown	0.94	1.031(0.47–2.261)
Adjuvant chemotherapy
No	Reference
Yes	0.004	0.498(0.309–0.802)	0.0001	0.34(0.195–0.595)
Unknown	0.447	0.806(0.462–1.405)	0.057	0.332(0.107–1.032)
Adjuvant radiotherapy
No	Reference
Yes	0.005	0.383(0.196–0.75)	0.028	0.424(0.197–0.916)
Unknown	0.913	1.027(0.637–1.657)	0.554	1.369(0.483–3.878)
KRT7
Low	Reference
High	0.001	2.095 (1.379–3.181)	0.006	1.87(1.2–2.915)

Table 3 Univariate and Multivariate Cox Regression Analysis of Disease-Free Survival in PAAD Patients

Variables	Univariate		Multivariate
	P value	HR (95% CI)	P value	HR (95% CI)
Age
<60	Reference
≥60	0.851	1.045(0.663–1.647)
Gender
Female	Reference
Male	0.578	0.883(0.57–1.369)
Histological type
Ductal type	Reference
Other subtype	0.007	0.407(0.213–0.78)	0.377	0.713(0.336–1.513)
Colloid carcinoma	0.997	–	0.998	–
Undifferentiated	0.998	–	0.999	–
Unknown	0.998	–	0.999	–
Grade
G1	Reference
G2	0.03	2.131(1.076–4.222)	0.202	1.595(0.779–3.265)
G3+G4	0.002	3.024(1.481–6.177)	0.101	1.858(0.886–3.894)
Gx	0.099	5.72(0.721–45.406)	0.135	5.276(0.594–46.6)
T classification
T1+T2	Reference
T3+T4	0.021	2.138(1.121–4.078)	0.962	1.026(0.359–2.926)
TX	0.997	–	1	–
Unknown	0.997	–	0.998	–
N classification
N0	Reference
N1	0.026	1.753(1.068–2.878)	0.284	1.421(0.747–2.704)
NX	0.995	–	0.998	–
Unknown	0.997	–	0.998	–
M classification
M0	Reference
M1	0.861	0.881(0.213–3.638)	0.998	0.997(0.08–12.48)
MX	0.005	0.521(0.329–0.825)	0.061	0.632(0.391–1.022)
Stage
I	Reference
II	0.014	2.688(1.217–5.937)	0.845	1.15(0.286–4.627)
III+IV	0.172	2.599(0.659–10.24)	0.872	1.217(0.111–13.31)
Unknown	0.995	–	–	–
Family history
No	Reference
Yes	0.818	1.065(0.62–1.831)
Unknown	0.84	1.059(0.605–1.855)
Chronic pancreatitis
No	Reference
Yes	0.623	0.776(0.282–2.137)
Unknown	0.371	0.737(0.378–1.438)
Diabetes history
No	Reference
Yes	0.817	0.933(0.52–1.674)
Unknown	0.126	0.561(0.268–1.176)
Alcohol history
No	Reference
Yes	0.307	1.284(0.795–2.073)
Unknown	0.525	0.732(0.279–1.919)
Adjuvant chemotherapy
No	Reference
Yes	0.997	1.001(0.583–1.719)
Unknown	0.797	1.1(0.532–2.276)
Adjuvant radiotherapy
No	Reference
Yes	0.551	0.849(0.495–1.455)
Unknown	0.807	0.927(0.502–1.711)
KRT7
Low	Reference
High	0.000	2.313(1.476–3.626)	0.019	1.793(1.097–2.933)

Figure 2 Prognostic significance of KRT7 in PAAD. (A-B) The prognostic significance of KRT7 expression in PAAD analyzed by GEPIA. (C-D) The prognostic significance of KRT7 expression in PAAD analyzed by PROGgeneV2.

Figure 3 The relationship between KRT7 expression and tumor grade (A) and TP53 mutations (B) in PAAD analyzed by UALCAN. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 4 Analysis of the difference in immune infiltration between the high and low KRT7 expression groups analyzed by ImmuCellAI. (A) The landscape of immune infiltration levels in TCGA-PAAD samples. (B) The difference of 24 immune infiltrating cells in the high and low KRT7 expression groups in PAAD.

Figure 5 The correlation between KRT7 expression with immunomodulators. (A-B) The correlation between KRT7 expression with immunoinhibitors and the top 2 immunoinhibitors showing the greatest correlation with KRT7 in PAAD. (C-D) The correlation between KRT7 expression with immunostimulators and the top 2 immunostimulators showing the greatest correlation with KRT7 in PAAD.

Figure 6 Genes correlated with KRT7 in PAAD analyzed by LinkedOmics. (A) All expressed genes correlated with KRT7 in PAAD. (B) Protein–protein interaction network and MCODE analysis of coexpressed genes. (C) Top 50 genes positively related to KRT7 in PAAD. (D) Top 50 genes negatively related to KRT7 in PAAD.

Figure 7 Survival analysis of 6 hub genes in PAAD performed by GEPIA. The results showed that KRT19, KRT16 and KRT17 were associated with the overall and disease-free survival rates in PAAD patients (P < 0.05).

Figure 8 Significant GO and KEGG terms of the coexpressed genes. (A) Biological process analysis of the coexpressed genes. (B) Cell component analysis of the coexpressed genes. (C) Molecular function analysis of the coexpressed genes. (D) KEGG pathway analysis of the coexpressed genes.

Figure 9 The biological functions of KRT7 and its related genes. (A) Protein–protein interaction network of KRT7 and its related genes analyzed by GeneMANIA. (B) Functional enrichment pathways of KRT7 and its related genes analyzed by Metascape. (C) Significant pathways in the data sets of high KRT7 expression analyzed by GSEA.